NCAM-mediated ßI spectrin expression and NMDA receptor trafficking

• Antragsteller: Dr. Vladimir Sytnyk
• Fachliche Zuordnung: Molekulare Biologie und Physiologie von Nerven- und Gliazellen
• Förderung: Förderung von 2004 bis 2013
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5427747

Formation of a synaptic contact between axon and dendrite is accompanied by accumulation of synaptic proteins and organelles at this site. The mechanisms that drive expression of synaptic proteins and accumulation of synaptic machinery at nascent synapses are poorly understood. Previously, we found that the neural cell adhesion molecule (NCAM) stabilizes formation and maintenance of synapses and determines expression and localization of betaI spectrin in CHO cells and hippocampal neurons. The cytoskeletal-membrane linker protein betaI spectrin is one of the major constituents of the postsynaptic density and may thus maintain synapse integrity. The proposed investigations will pursue two aims. First, we would like to study the role of NCAM in anchoring of betaI spectrin at sites of interneuronal contacts during early stages of synaptogenesis in culture and investigate the effect of the NCAM-to-betaI spectrin association on synaptic accumulation of spectrin-associated NMDA receptors by biochemical and immunocytochemical methods and video timelapse recording in wild-type and NCAM-deficient neurons. The second aim of this study is the analysis of the mechanisms of NCAM-induced betaI spectrin expression. On the basis of our finding that levels of betaI spectrin protein were increased in cells expressing the NCAM isoforms NCAM120, NCAM140 or NCAM180 versus cells not expressing NCAM, we want to identify the signalling pathways, including transcription factors, that regulate NCAM-activated expression of spectrin isoforms. Subcellular localization of betaI spectrin mRNA will be analyzed by means of in situ hybridization in wild-type and NCAM-deficient hippocampal neurons to study a potential role of NCAM in determining local and, in particular synaptic, betaI spectrin synthesis.

• DFG-Verfahren: Sachbeihilfen
• Beteiligte Personen: Dr. Iryna A. Leshchynska; Professorin Dr. Melitta Schachner